Michaels hit a two-run homer in the 10th inning, the Pirates' third big homer in three innings, and Pittsburgh rallied from six runs down in the eighth to beat the St. Louis Cardinals 12-11 Saturday night.
"What a game," the Pirates' Adam LaRoche said. "You don't see games like that very often."
The Cardinals appeared to be cruising with a season-high 22 hits while taking leads of 9-3 in the seventh and 10-4 in the eighth, but Jason Bay hit his second two-run homer of the night in the eighth.
"We're still up by one [after McLouth's homer], but we couldn't get it done," Isringhausen said. "It didn't seem like it mattered what we threw up, they got a hit or something weird happened."
Troy Glaus homered leading off the 10th for St. Louis' 10th extra-base hit, but the Cardinals' unreliable bullpen couldn't hold this lead, either. Cardinals relievers have lost 20 games and lead the majors with 22 blown saves.
"It was one of the more amazing games I've ever been involved in," Bay said. "That was something I'll never forget. Early on, it kind of felt like we were down by 10. You get a hit here, a homer, and you say, 'OK, OK, we've got some momentum' and that's when you start to feel it. Nate comes up and, boom, that puts you within one run."
The Cardinals outhit the Pirates 22-13 but left 12 on base.
"It's one of those games that got away, but the Pirates have done it to us a couple, three times," manager Tony La Russa said. "We know they're going to play nine innings -- and 10."
The Pirates are five games under .500 at 44-49, but are 10-3 in extra innings with eight consecutive victories, a streak that began when they rallied to win 8-4 at St. Louis in 10 innings on May 13. Michaels hit a grand slam in St. Louis to cap a comeback from a 4-0 deficit as the Pirates won 5-4 on June 2.
"But this is definitely No. 1," Michaels said. "I've never had a walk-off homer. That was awesome."
Raul Chavez singled to start the Pirates' 10th against Kyle McClellan, who was lifted for rookie Chris Perez (2-1). Michaels, who entered the game as a pinch-hitter in the ninth and drew a key walk ahead of McLouth's homer, followed a batter later with a drive into the left-center seats for his fourth homer.
Denny Bautista (3-1) got the victory despite allowing Glaus' 14th homer. Glaus went 4-for-4 and reached base six times, walking twice.
The Cardinals fell 5½ games behind NL Central leader Chicago despite totaling 17 runs and 35 hits in the first two games of the three-game series. They had scored more than two runs only once in their previous seven, getting outscored 32-13 while losing five of those seven.
Offense wasn't the Cardinals' problem as NL All-Star Ludwick went 3-for-5 with four RBIs, Albert Pujols and Rick Ankiel each doubled twice and Yadier Molina went 4-for-6, giving him six hits in two nights and raising his average to .313.
The Cardinals easily topped the 16 hits they had several times previously this season.
"It's unfortunate we got beat in a game we scored  runs," La Russa said. "Today we scored but we couldn't pitch."
The Pirates' rally cost Todd Wellemeyer his first victory since June 5 after he allowed four runs in 6 1/3 innings. He hadn't lasted past the fifth inning in his previous four starts.
Much of the Cardinals' big night came against right-hander Yoslan Herrera, a former Cuban national pitcher who was recalled from Double-A Altoona. He yielded 11 hits and six runs in 4 1/3 innings in his major league debut.
Herrera signed a $1.92 million, three-year contract before the 2007 season, but had not pitched in the majors until Saturday.
Bay's two-run drive in the first gave Herrera a 2-0 lead, but he quickly gave it back by allowing six hits in a span of nine batters as St. Louis scored three times in the third and twice in the fourth.
Pirates third baseman Doug Mientkiewicz was ejected by umpire Eric Cooper in the fourth for running across the infield to argue that Pujols was out at second on a double down the line that eluded Mientkiewicz. The Pirates trailed 5-2 at the time.
Ankiel is 11-for-28 (.393) with eight RBIs in seven games but was lifted after turning his left ankle while batting in the seventh. The injury isn't believed to be serious, and he was removed mostly for precautionary reasons. ... Wellemeyer, batting eighth as La Russa does with his pitchers, had a sacrifice bunt but left six runners on base while going 0-for-3. ... It could have been worse for Herrera: The Cardinals failed to score despite having the bases loaded with none out in the second.